Friday, June 28, 2013

Origin of the genetic code

I am curious about the origin of the genetic code, as distinct from the discovery of the chemical structure of DNA. The UK Telegraph reports:

That enigma was resolved in 1953, in two scientific articles by James Watson and Francis Crick of the University of Cambridge. First, they suggested that the DNA molecule was composed of two parallel spirals that were mirror images of each other, with the sequence of bases on one spiral being matched by the sequence on the other – the double helix. Then, five weeks later, they boldly stated that “the precise sequence of the bases is the code which carries the genetical information”. They argued that the DNA molecule contained a code that told the cell what protein to make.

Immediately, the physicist George Gamow suggested that the code must use sequences of three “letters” or bases. Given that there were 20 amino acids, a two-base code would not work (there are only 16 possible two-letter combinations of the four bases). A three-base code would produce 64 possible combinations – easily enough to encode the 20 amino acids.

It had been previously suggested by researchers such as Dounce (1952) and Caldwell and Hinshelwood (1950) that the order of the bases might in some way enable a gene to synthesise proteins, probably by acting as a physical template (Dounce even argued that three bases would correspond to a particular amino acid, which turned out to be right, but not for the physico-chemical reasons that Dounce argued). In 1950, Erwin Chargaff had suggested that a single change in a base could lead to a mutation, but again he viewed this in terms of a physical change to the DNA molecule.

The great step forward made by Watson and Crick in their second paper was to take these pre-existing ideas and reshape them in a less literal form. The sequence of bases was no longer seen in terms of a physical template for protein synthesis, but as something far more abstract – a code carrying genetical information.

Watson and Crick with their model of the DNA molecule. Crick is pointing with a slide-rule. Note the sketch of the double helix, by Crick’s wife Odile, pinned to the wall.

What is intriguing is where this novel interpretation came from. The first person who explicitly suggested that genes contained a ‘code-script’ was the physicist Erwin Schrödinger, in 1943. Although his ideas were widely-read, there were few attempts to explore the idea of a ‘code’, because the physical nature of the gene was unknown.

Watson was here as an undergraduate, and was first interested in ornithology. He said his interests changed when he read Erwin Schrödinger’s 1944 book What is Life?, which inspired many biologists to work on the molecular basis of inheritance.

So maybe Watson got it from Schroedinger. Here is what that 1944 book said:

“It is these chromosomes, or probably only an axial skeleton fibre of what we actually see under the microscope as the chromosome, that contain in some kind of code-script the entire pattern of the individual's future development and of its functioning in the mature state. Every complete set of chromosomes contains the full code; so there are, as a rule, two copies of the latter in the fertilized egg cell, which forms the earliest stage of the future individual.”

This seems to be a pretty clear explanation of the concept of chromosomes carrying a genetic code.

Linus Pauling had similar ideas and could have found it all by himself. From what little I remember and surmise from my readings, Watson played up his role in finding the DNA structure. Fortunately Francis Crick was not a querulous man. Crick went on to make many other important discoveries connected to DNA/RNA, Watson did not; which leads me to suspect that it was Crick who did the heavy lifting in 1953.